Developmental changes in angiotensin II receptor subtypes and AT1 receptor mRNA in rat kidney

Abstract

The changes in angiotensin II receptor subtypes, type 1 (AT1) and type 2 (AT2) binding, and AT1 mRNA levels during development were studied in the rat kidney using autoradiographic and in situ hybridization techniques. Autoradiographic analysis of 125I-[Sar1,Ile8]Ang II binding to slide-mounted kidney sections from 2 and 5 day-old rats discerned AT2 binding sites associated with advancing tubules and ampullae of the ureteric bud, and in the metanephric mass in the nephrogenic zone of the cortex. AT1 binding was present in the metanephric mass and immature glomeruli on days 2, 5 and 7 after birth. Differentiating and mature kidneys of 14-day, 21-day and 14-week old adult rats had solely AT1 receptor binding over glomeruli in renal cortex and in the inner stripe of the outer medulla. AT1 mRNA was expressed discretely as early as 2 days of age in the immature glomeruli and in a diffuse radiating pattern in the renal cortex. In the medulla, AT1 receptor mRNA expression appeared discretely on day 7 and reached peak levels on day 21 in the inner stripe of the outer medulla. The data indicate that AT1 receptor mRNA is developmentally regulated in rat kidney and its expression in the cortex precedes that of AT1 receptor ligand binding. The temporal pattern of expression of binding for both receptor subtypes suggests that while AT2 receptors may be involved in cell proliferation and early differentiation of the nephron, AT1 receptors have a dual role, early in nephron differentiation and later in development in renal function.